Summary
Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to ...life‐threatening immediate‐type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate‐type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross‐sensitization to PEGylated drugs and structurally related derivatives is likely underestimated. Most healthcare professionals have no knowledge of PEG and thus do not suspect PEG's as culprit agents in hypersensitivity reactions. In consequence, patients are at risk of misdiagnosis and commonly present with a history of repeated, severe reactions to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re‐exposure. This first comprehensive review provides practical information for allergists and other healthcare professionals by describing the clinical picture of 37 reported cases of PEG hypersensitivity since 1977, summarizing instances where PEG hypersensitivity should be considered and proposing an algorithm for diagnostic management.
Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test ...concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.
Abstract
Background.
Propofol is thought to be a potential cause of allergic reactions in patients allergic to egg, soy or peanut, since current formulations contain an emulsion that includes egg ...lecithin and soybean oil. However, other than six case reports lacking in confirmatory evidence of an allergic reaction, there is no evidence linking the two types of allergies. The aim of this study was to examine the frequency of propofol allergy and to investigate if patients with specific immunoglobulin E (IgE) to egg, soy or peanut tolerated propofol.
Methods.
Study A examined the frequency of propofol allergy in 273 patients systematically investigated for suspected perioperative allergic reactions. Of these, 153 had been exposed to propofol and underwent skin tests and intravenous provocation. Study B retrospectively investigated propofol exposure and tolerance in 520 adult patients with a positive specific IgE to egg, soy or peanut.
Results.
Four of the 153 propofol-exposed patients (2.6%) investigated in study A were diagnosed with propofol allergy. Of these, three tested positive only on intravenous provocation. None of the four had allergic symptoms when eating egg, soy or peanut and none had detectable levels of specific IgE to egg or soy in their serum. In study B we found no signs of allergic reactions towards propofol in 171 retrieved anaesthetic charts from 99 patients with specific IgE to egg, soy or peanut.
Conclusion.
No connection between allergy to propofol and allergy to egg, soy or peanut was found. The present practice of choosing alternatives to propofol in patients with this kind of food allergy is not evidence based and should be reconsidered.
To cite this article: Johansson SGO, Florvaag E, Öman H, Poulsen LK, Mertes PM, Harper NJN, Garvey LH, Gerth van Wijk R, Metso T, Irgens A, Dybendal T, Halsey J, Seneviratne SL, Guttormsen AB. ...National pholcodine consumption and prevalence of IgE‐sensitization: a multicentre study. Allergy 2010; 65: 498–502.
Background: The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO‐containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased.
Methods: National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P‐aminophenyl‐phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop® test (>0.35 kUA/l), collected in nine countries representing high and low PHO‐consuming nations.
Results: There was a significant positive association between PHO consumption and prevalences of IgE‐sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO‐containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE‐sensitization.
Conclusion: This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE‐sensitization towards NMBAs.
The present approach to the diagnosis, management and follow‐up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice ...Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia.
The recommendations are based on the best available evidence in the literature, which, owing to the rare and unforeseeable nature of anaphylaxis, mainly includes case series and expert opinion (grade of evidence IV and V).
These guidelines include an overview of the epidemiology of anaphylactic reactions during anaesthesia. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline (epinephrine) and fluid therapy as first‐line treatment.
Recommendations for primary and secondary follow‐up are given, bearing in mind that there are variations in geography and resources in the different countries. A list of National Centres from which anaesthesiologists can seek advice concerning follow‐up procedures is provided. In addition, an algorithm is included with advice on how to manage patients with previous suspected anaphylaxis during anaesthesia. Lastly, Appendix 2 provides an overview of the incidence, mechanisms and possibilities for follow‐up for some common drug groups.
Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an ...immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents.
We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1–9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated.
Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase.
We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.
Background
Perioperative allergic reactions to chlorhexidine are often severe and easily overlooked. Although rare, the prevalence remains unknown. Correct diagnosis is crucial, but no validated ...provocation model exists, and other diagnostic tests have never been evaluated. The aims were to estimate (i) the prevalence of chlorhexidine allergy in perioperative allergy and (ii) the specificity and sensitivity for diagnostic tests for chlorhexidine allergy.
Methods
We included all patients investigated for suspected perioperative allergic reactions in the Danish Anaesthesia Allergy Centre during 2004–2012. The following tests were performed: specific IgE (Immunocap®; Phadia AB, Sweden), histamine release test (HR) (RefLab ApS, Denmark), skin prick test (SPT) and intradermal test (IDT). Positivity criteria were as follows: specific IgE >0.35 kUA/l; HR class 1–12; SPT mean wheal diameter ≥3 mm; IDT mean wheal diameter ≥ twice the diameter of negative control. Chlorhexidine allergy was post hoc defined as a relevant clinical reaction to chlorhexidine combined with two or more positive tests. Based on this definition, sensitivity and specificity were estimated for each test.
Results
In total, 22 of 228 patients (9.6%) met the definition of allergy to chlorhexidine. Estimated sensitivity and specificity were as follows: specific IgE (sensitivity 100% and specificity 97%), HR (sensitivity 55% and specificity 99%), SPT (sensitivity 95% and specificity 97%) and IDT (sensitivity 68% and specificity 100%).
Conclusions
In patients investigated for suspected perioperative allergic reactions, 9.6% were diagnosed with allergy to chlorhexidine. Using our definition of chlorhexidine allergy, the highest combined estimated sensitivity and specificity was found for specific IgE and SPT.
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